This application claims the priority of Japanese Patent Application No. 11-27604 filed on Feb. 4, 1999, which is incorporated herein by reference.
The present invention relates to a (2-substituted oxyphenyl)alkanamide derivative and, in particular, to a (2-substituted oxyphenyl)alkanamide derivative that has excellent hair growth effect.
At the present time, scalp abnormality due to activation of androgen in an organ such as hair root or sebaceous gland, lowering of blood stream toward hair follicle, excess secretion of sebum, formation of peroxide and the like has been considered as a cause of baldness or hair loss. Accordingly, a compound or composition that can remove or reduce the above-mentioned problems has been generally included into a hair growth promoting composition to promote hair growth and regrowth and to prevent hair loss, for a long time (in the present invention, xe2x80x9chair growth promoting compositionxe2x80x9d includes hair regrowth promoting composition, and the like).
At present, compounds or crude drug extracts having various functions have been compounded to the hair growth promoting composition. These functions include blood flow promoting action, topical stimulation, hair follicle activating action, antiandrogen action, antiseborrheic action and the like have been known. Examples of drugs having blood flow promoting action include swertia herb extract, vitamin E and its derivative, and benzyl nicotinate. Examples of drugs which promote blood circulation by topical stimulation include capsicum tincture, cantharides tincture, camphor and vanillic acid nonylamide. Examples of drugs having hair follicle activating action include hinokitiol, placental extract, photosensitizing dye, pantothenic acid and derivative thereof. Examples of drugs having antiandrogen action include estradiol and estrone. Examples of drugs having antiseborrheic action include sulfur, thioxolone and vitamin B6.
In addition to these drugs, salicylic acid, resorcine and the like that have corneocyte desquamating action and antibacterial action can be compounded to hair growth promoting composition for the purpose of preventing dandruff. Further, glycyrrhizic acid, menthol and the like can be compounded in order to prevent inflammation of scalp. Furthermore, amino acids, vitamins, extracts of crude drugs and the like can be compounded so as to aliment to hair follicle and activate enzyme activity.
Meanwhile, for example, D (L)-pantolactone (Unexamined Japanese Patent Publication No. Hei 8-26942), 2(1H)-pyridone derivative (Unexamined Japanese Patent Publication No. Hei 8-20521), NG-nitro-L-arginine (Unexamined Japanese Patent Publication No. Hei 7-316023), 3-methyleneisoindolin-1-one derivative (Unexamined Japanese Patent Publication No. Hei 7-316022), indole derivative (Unexamined Japanese Patent Publication No. Hei 7-304736) are disclosed in recent patents as drugs having hair regrowth effect, hair growth effect, and hair loss protecting effect.
However, although the drugs described above are compounded to the conventional hair growth promoting compositions, they do not always exhibit sufficient hair regrowth and growth promoting effect.
In view of the foregoing problem in the prior art, an object of the present invention is to provide a compound, which is excellent in hair growth and regrowth promoting effect on human hair, and a hair growth promoting composition comprising the same as an active ingredient.
As a result of diligent studies of the inventors for attaining the above mentioned objects, it has been found that certain (2-substituted oxyphenyl)alkanamide derivative and its salt have excellent hair growth and regrowth promoting effect, thereby accomplishing the present invention.
Namely, a (2-substituted oxyphenyl)alkanamide derivative or a salt thereof in accordance with the present invention is expressed by the following Formula (I): 
wherein each of A and B is R1 or xe2x80x94(CH2)n-NR2R3, wherein when A is R1, B is xe2x80x94(CH2)n-NR2R3 and when A is xe2x80x94(CH2)n-NR2R3, B is R1;
Z is xe2x80x94COxe2x80x94 or xe2x80x94CONR6xe2x80x94;
R1 is a hydrocarbon group of C3-30;
R2 and R3 individually represent a hydrogen atom, a lower alkyl group or a benzyl group, or xe2x80x94NR2R3 may be a heterocycle having 3-7 members; wherein when B is xe2x80x94(CH2)nxe2x80x94NR2R3 or when xe2x80x94(Z)1xe2x80x94A is xe2x80x94CONR6xe2x80x94(CH2)n-NR2R3, said xe2x80x94CONR5xe2x80x94(CH2) n-NR2R3 and said xe2x80x94CONR6xe2x80x94(CH2)n-NR2R3 may be expressed by the following Group (II): 
wherein ring Y is a heterocycle of 6 or 7 members including two nitrogen atoms, and R2is a hydrogen atom, a lower alkyl group or a benzyl group;
R4 is selected from the group consisting of a hydrogen atom, a halogen atom, a lower alkyl group, a lower acyl group, a nitro group, a cyano group, a lower alkoxycarbonyl group, a carbamoyl group, a lower alkylcarbamoyl group, a lower alkylamino group, a lower acylamino group, a lower alkoxy group and a lower acyloxy group;
R5 is a hydrogen atom, a lower alkyl group, a lower acyl group or a lower alkylcarbamoyl group; wherein when B is xe2x80x94(CH2)n-NR2R3, xe2x80x94CONR5xe2x80x94(CH2)n-NR2R3 may be said Group (II);
R6 is a hydrogen atom, a lower alkyl group, a lower acyl group or a lower alkylcarbamoyl group; wherein when xe2x80x94(Z)1xe2x80x94A is xe2x80x94CONR6xe2x80x94(CH2)n-NR2R3, xe2x80x94CONR6xe2x80x94(CH2)nxe2x80x94NR2R3 may be said Group (II);
1 is 0 or 1;
m is 1 or 2; and
n is an integer of 0-5.
A hair growth promoting composition in accordance with the present invention is characterized by comprising said (2-substituted oxyphenyl)alkanamide derivative or the pharmacologically acceptable salt thereof as an effective ingredient.
An external preparation for skin in accordance with the present invention is characterized by comprising said (2-substituted oxyphenyl)alkanamide derivative or the pharmacologically acceptable salt thereof.
A method for promoting hair growth in accordance with the present invention is characterized by applying an effective amount of said (2-substituted oxyphenyl)alkanamide derivative or the pharmacologically acceptable salt thereof on the skin of mammals and, in particular, on human scalp.